Is CD151 p.Glu6Lys (c.16G>A) pathogenic?

CD151 p.Glu6Lys (c.16G>A) is classified Uncertain significance in CD151 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-13). AlphaMissense: likely benign (0.0975); Ultra-rare (popmax 0.0468%, eas); Associated with RAPH BLOOD GROUP SYSTEM.

What condition is associated with CD151 p.Glu6Lys (c.16G>A)?

CD151 p.Glu6Lys (c.16G>A) is associated with RAPH BLOOD GROUP SYSTEM, epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Glu6Lys (c.16G>A) in the general population?

CD151 p.Glu6Lys (c.16G>A) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

What do computational predictors say about CD151 p.Glu6Lys (c.16G>A)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

CD151 p.Glu6Lys

c.16G>A · rs371206840 · VCV1408948

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RAPH BLOOD GROUP SYSTEM

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,119 bp · p 0.3 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0468% East Asian · 21/44,896 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00726% 117/1,612,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0468%	2,138
European (non-Finnish)	0.00755%	13,251
Remaining individualsnot grpmax-eligible	0.0048%	20,813
African / African-American	0.00267%	37,448
South Asian	0.0022%	45,528

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD151
Protein: p.Glu6Lys
Coding: c.16G>A
MANE Select: NM_004357
dbSNP: rs371206840
Type: single nucleotide variant
Location: chr11:836085 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.02

Full CD151 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RAPH BLOOD GROUP SYSTEM — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 7, with nephropathy and deafness

Similar variants

CD151 p.Lys7Ter Pathogenic ★★ same condition
CD151 c.352-11C>G Uncertain significance ★★ same condition
CD151 c.702+4A>G Uncertain significance ★★ same condition
CD151 c.702+5G>C Uncertain significance ★★ same condition
CD151 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
CD151 p.Ala81Thr Uncertain significance ★★ ⚠ same condition
CD151 p.Arg133Cys Uncertain significance ★★ ⚠ same condition
CD151 p.Arg165Gln Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd151-p-glu6lys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown